Apalutamide radio-sensitisation of prostate cancer

Kakouratos, Christos; Kalamida, Dimitra; Lamprou, Ioannis; Xanthopoulou, Erasmia; Nanos, Christos; Giatromanolaki, Alexandra; Koukourakis, Michael I.

doi:10.1038/s41416-021-01528-1

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…While previous studies have demonstrated that AR inhibitors can radiosensitise AR+ models of TNBC, prostate cancer and glioblastoma [ 7 , 8 , 16 , 25 , 27 , 45 , 46 ], in this study we demonstrate that pharmacologic inhibition, degradation, or genetic knockout of AR using CRISPR-Cas9, is not sufficient to radiosensitise AR+/ER+ breast cancer cell lines in vitro (Figs. 1 , 2 , 4 , Supplementary Fig.…”

Section: Discussioncontrasting

confidence: 67%

“…Androgen receptor expression has also been investigated as a contributor to the radiation response in multiple types of cancer, including prostate cancer, breast cancer and glioblastoma [ 8 – 12 ]. AR has been shown to be a mediator of radioresistance in prostate cancer [ 23 ], and inhibition of AR with apalutamide results in an increased radiosensitivity through a decrease in non-homologous end-joining (NHEJ) efficiency [ 24 , 25 ]. Additionally, in AR+ glioblastoma cell lines and xenograft models, inhibition of AR with enzalutamide or seviteronel has been shown to provide sensitisation to radiation therapy [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

et al. 2022

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Purpose Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about the interaction of the androgen receptor (AR) and estrogen receptor (ER) in response to RT in AR-positive, ER-positive (AR+/ER+) breast cancers. Here we assessed radiosensitisation of AR+/ER+ cell lines using pharmacologic or genetic inhibition/degradation of AR and/or ER. Methods Radiosensitisation was assessed with AR antagonists (enzalutamide, apalutamide, darolutamide, seviteronel, ARD-61), ER antagonists (tamoxifen, fulvestrant) or using knockout of AR. Results Treatment with AR antagonists or ER antagonists in combination with RT did not result in radiosensitisation changes (radiation enhancement ratios [rER]: 0.76–1.21). Fulvestrant treatment provided significant radiosensitisation of CAMA-1 and BT-474 cells (rER: 1.06–2.0) but not ZR-75-1 cells (rER: 0.9–1.11). Combining tamoxifen with enzalutamide did not alter radiosensitivity using a 1 h or 1-week pretreatment (rER: 0.95–1.14). Radiosensitivity was unchanged in AR knockout compared to Cas9 cells (rER: 1.07 ± 0.11), and no additional radiosensitisation was achieved with tamoxifen or fulvestrant compared to Cas9 cells (rER: 0.84–1.19). Conclusion While radiosensitising in AR + TNBC, AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer. The efficacy of ER antagonists in combination with RT may also be dependent on AR expression.

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Section: Discussioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

et al. 2022

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“…Apalutamide can effectively kill prostate tumor cells in 1 day ( 30 ). Adding excess testosterone to the 22Rv1 cell line mimics the “testosterone rebound phenomenon”, apalutamide can significantly enhance the lethality of radiotherapy and has a concentration-dependent property ( 31 ),and also significantly up-regulate the expression of AR, PSA, TMPRSS2, etc., while there is no obvious response in CRPC cell lines such as PC3 and DU145 ( 14 ). Chris Tran, the inventor of apalutamide, has already reported ( 11 ): In vitro cell experiments, apalutamide significantly reduced PSA mRNA levels in LNCaP/AR cells for 8 hours.…”

Section: Discussionmentioning

confidence: 99%

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

Liu²,

Chen³

et al. 2022

Front. Oncol.

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ObjectiveTo examine the effects of apalutamide on endocrine function and flare prevention in metastatic hormone-sensitive prostate cancer (mHSPC) patients administered GnRH agonists.MethodsThe first newly diagnosed mHSPC patient took apalutamide for 2 weeks followed by combination with GnRH agonist, as recommended by clinical guidelines. Serum luteinizing hormone (LH), testosterone, and PSA were detected during the oral administration of apalutamide before and after ADT. Eight newly diagnosed mHSPC patients innovatively took apalutamide 1 hour before GnRH agonist administration; LH, testosterone and PSA were detected before and after ADT.ResultsIn the first patient, LH and testosterone levels were increased during apalutamide monotherapy, and serum PSA levels decreased rapidly, demonstrating apalutamide effectively blocked AR signaling. In patients on the 1-hour regimen, combined treatment with apalutamide and GnRH agonists led to peak level of testosterone on day 3 and castration level on day 28, while PSA decreased continuously. No one experienced dysuria or bone pain worsen after ADT.ConclusionTaking apalutamide 1 hour in advance may effectively prevent the flare-up effect in prostate cancer patients treated with GnRH agonists. Compared with the 2-week regimen, the 1-hour regimen could simplify the treatment process and bring testosterone to castration levels in advance.

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Failure to progress: breast and prostate cancer cell lines in developing targeted therapies

James,

Whitehead,

Plummer

et al. 2024

Cancer Metastasis Rev

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Apalutamide radio-sensitisation of prostate cancer

Cited by 5 publications

References 28 publications

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

Failure to progress: breast and prostate cancer cell lines in developing targeted therapies

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